The development of new scaffolds and their processing into complex structures are becoming increasingly important for the repair and regeneration of tissues and are a key step to tissue engineering advances for ultimate clinical application. The hypothesis of this R15 proposal is that a bioactive scaffold combining mechanical support with biological activity may be formed from hollow hydroxyapatite (HA) microspheres. The focus of the work is to explore key steps in the development of scaffolds for eventual application to tissue engineering of the periodontium, but the results are expected to have additional wider applications to tissue engineering. Our preliminary work showed that hollow HA microspheres can be formed at near room temperature by reacting borate glass microspheres in an aqueous phosphate solution, and that the release of an encapsulated protein, bovine serum albumin, from the microspheres into a surrounding medium of phosphate buffered saline (PBS) is controllable by altering the porosity of the hollow microsphere wall. Our approach will be to (1) comprehensively characterize the structure and mechanical properties of hollow HA microspheres formed from borate glass, and (2) evaluate the controlled release and biological activity of a growth factor from the microspheres into a surrounding medium. Bone morphogenetic protein (BMP-2) is chosen as the growth factor because of its potent ability to induce osteogenesis and cementum formation, two of the multiple processes involved in periodontal repair. Our long-term goal is to fabricate composite scaffolds of hollow HA microspheres which allow tailoring of the mechanical properties, release of multiple growth factors, cellular infiltration, and integration with surrounding tissue, for eventual application to engineering of periodontal and other tissues. The present R15 project will provide important information on the structure and mechanical properties of these hollow HA microspheres and the value of the microspheres for use in the delivery of growth factors. The in vitro studies are anticipated to lead to a larger application (R01), involving multiple campuses, in which engineering of the periodontium will be intensely investigated in vivo as a function of delivery of growth factors from composite constructs containing hollow HA microspheres. Additional goals to be pursued in conjunction with the research are (1) exposure of graduate and undergraduate students to cross-disciplinary research in materials science and biological sciences, which is critical to the development of new and improved biomaterials, and (2) strengthening current and future efforts in biomedical research and education at the University of Missouri-Rolla. Periodontal disease is one of the most common infectious diseases in the world, affecting virtually all adults to some degree. Several periodontal diseases lead to the loss of teeth as a major organ in the craniofacial region, and severe compromise in physiological function. Tissue engineering approaches, based on cell or growth factor delivery from biomaterials scaffolds, offer promising solutions for complete regeneration of the periodontium. [unreadable] [unreadable] PUBLIC HEALTH RELEVANCE: Periodontal disease is one of the most common infectious diseases in the world, affecting virtually all adults to some degree. Several periodontal diseases lead to the loss of teeth as a major organ in the craniofacial region, and severe compromise in physiological function. Tissue engineering approaches, based on cell or growth factor delivery from biomaterials scaffolds, offer promising solutions for complete regeneration of the periodontium. [unreadable] [unreadable] [unreadable] [unreadable]